This project is aimed at evaluating the efficacy of a novel non-nucleosidic reverse transcriptase (NNRT)-inhibitor at i) lowering viral loads in disseminated infection and ii) preventing the establishment of infection by early treatment onset post infection in collaboration with the Tsukuba Primate Center in Japan and Bayer AG (Yahukin, Japan). Since this drug is specific for HIV-1 RT and does not inhibit SIV-RT, a chimeric virus was developed where the HIV-1 Hxb2 RT gene replaced the SIVmac239 RT gene. Preliminary data established the infectious potential of the isolate and the efficacy of the NNRT inhibitor (IC90) alone or in combination in vitro. Toxicitiy studies were also performed by testing the effect of the compound on various cell mediated immune functions in vitro. Phase 1 of the animal experiment conducted at Yerkes was aimed at characterizing the animal infectious doses of the SHIV-RT stock, the kinetics of viral loads and virulence of the SHIV-RT isolate in vivo. Three groups of 2 macaques each were administered 100, 10 or 1 TCID50 of the SHIV-RT I.V. and the animals were monitored for plasma and cellular viral loads, phenotypic profiles and clinical symptoms. All animals became infected and after resolution of the acute infection, treatment with the NNRT inhibitor was initiated for a total of 4 weeks to evaluate the induced decrease in viral loads. Phase 2 of the animal experiment to be conducted at Yerkes will use 3 groups of 3 macaques each to evaluate the potential of the NNRT inhibitor at preventing the establishment/dissemination of SHIV infection by initiating treatment 24 to 72 hours post infection.